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FUTURE DIRECTIONS S241

Proton (1H) MR Spec-

troscopy of the Breast1
Lia Bartella, MD ● Wei Huang, PhD
TEACHING
POINTS
See last page Proton (hydrogen 1) [1H]) magnetic resonance (MR) spectroscopy
provides biochemical information about the tissue under investigation.
Its diagnostic value in cancer is typically based on the detection of el-
evated levels of choline compounds, choline being a marker of active
tumor. The two main potential clinical applications of 1H MR spec-
troscopy are (a) as an adjunct to breast MR imaging to improve speci-
ficity in differentiating benign from malignant lesions, and (b) for
monitoring or even predicting response to treatment in patients under-
going neoadjuvant chemotherapy. Preliminary data are promising, with
study results suggesting that 1H MR spectroscopy may decrease the
number of benign biopsies recommended on the basis of MR imaging
findings and may help predict response as early as 24 hours after the
first dose of neoadjuvant chemotherapy. Although several limitations
currently exist that make the technique premature for clinical use, fur-
ther evaluation with larger, preferably multicenter trials is certainly
warranted.
©
RSNA, 2007

Abbreviations: DCIS ⫽ ductal carcinoma in situ, PPV ⫽ positive predictive value, SNR ⫽ signal-to-noise ratio

RadioGraphics 2007; 27:S241–S252 ● Published online 10.1148/rg.27si075504 ● Content Codes:

1From the Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021. Received February 5, 2007;
revision requested March 15 and received May 16; accepted June 21. Both authors have no financial relationships to disclose. Address correspon-
dence to L.B. (e-mail: liabartella@hotmail.com).
©
RSNA, 2007
 S242 October 2007
Introduction
Proton (hydrogen 1) [1H]) magnetic resonance
(MR) spectroscopy is not a new technology, hav-
ing been used to provide biochemical information
about biologic tissues for over 30 years. 1H MR
spectroscopy has been approved by the U.S.
Food and Drug Administration and is widely
used for evaluation of the brain and prostate
gland. Overall, however, its evolution has been
slow in the clinical setting and even slower in
breast studies. Although quantification of me-
tabolite levels is routinely performed in 1H MR
spectroscopy of the brain, it is more difficult to
perform in breast evaluation because of the hetero-
geneous distribution of the glandular and adipose
tissues (1). With respect to the breast, 1H MR
spectroscopy is still an investigational technique
with a promising future in the clinical setting.
The diagnostic value of 1H MR spectroscopy
Teaching in cancer is typically based on the detection of
Point elevated levels of choline compounds, choline
being a marker of active tumor (2). These com-
pounds have methyl protons that resonate at a
chemical shift of 3.2 ppm (3). The composite
resonance at 3.2 ppm includes contributions from
choline, phosphocholine, glycerophosphocholine,
myoinositol, and taurine (4).
In this article, we review 1H MR spectroscopic
technique; discuss and illustrate the potential
clinical applications of this modality in the breast
(differentiating benign from malignant breast le-
sions, predicting response to neoadjuvant chemo-
therapy); and describe the current limitations of
1H MR spectroscopy in this setting.
Technical Considerations
Breast 1H MR spectroscopy is usually performed
on a clinical magnet with a field strength of at
least 1.5 T. A breast coil is also needed, just as for
MR imaging. Spectroscopic sequences are com-
mercially available, but at the present time, a
spectroscopist needs to be involved to perform
off-line data processing.
Breast 1H MR spectroscopy has predominantly
been performed with a single-voxel technique.
This technique is limited to evaluating one lesion
at a time. A voxel is placed to encompass the le-
sion or area of interest. In most single-voxel 1H
MR spectroscopic studies of the breast, the point-
resolved spectroscopic sequence or a variation
thereof is used for data acquisition. One such
variation is the incorporation of echo time averag-
ing technique into a regular point-resolved spec-
troscopic sequence (1). This method reduces the
sidebands that result from spurious echoes gener-
RG f Volume 27 ● Special Issue
ated by mobile lipids, which sidebands can ob-
scure the detection of the choline peak. This lipid
signal problem arises because of the large amount
of fat in the breast. Typical acquisition parame-
ters include an echo time of 135 msec or longer to
reduce lipid signal and a repetition time of 1.5–
3.0 seconds. The number of signals acquired is
usually between 128 and 256, resulting in a net
data acquisition time of 3.2–12.8 minutes. An
extra 5–10 minutes is needed for preacquisition
set-up of 1H MR spectroscopy voxel shimming
and water suppression. In cases of multiple sus-
pect lesions in one breast, multivoxel MR spec-
troscopy is the preferred technique. This tech-
nique provides information about the spatial dis-
tribution of metabolites and is useful for studying
multiple lesions. It can be used to measure multi-
regional metabolite levels in a data acquisition
time comparable to that for a single-voxel study.
However, mostly due to difficulty in obtaining
good shimming in a relatively large breast region
within a reasonable time frame, only a few studies
have yielded data of acceptable quality (5,6). For
differentiating benign from malignant breast le-
sions, except for a study in which choline concen-
tration was quantified using water signal as the
internal reference (1), the majority of 1H MR
spectroscopic studies are based on detection (or
nondetection) of the choline peak or its signal-to-
noise ratio (SNR) (7).
Breast 1H MR spectroscopy has several draw-
backs. Prior contrast material– enhanced MR im-
aging is usually required for lesion localization
and MR spectroscopic voxel placement. The ac-
cumulation of contrast agent in the lesion can
affect 1H MR spectroscopic quality due to T2*
broadening effect (8). Also, the time required (in-
cluding preacquisition adjustment) is relatively
long (10 –25 minutes) and the spatial resolution
poor. Fine tumor heterogeneity cannot be as-
sayed. It is difficult to achieve sufficient simulta-
neous suppression of water and lipid resonances,
making it difficult to quantify choline concentra-
tion. Thus, the majority of 1H MR spectroscopic
studies are non- or semiquantitative. Further-
more, because of the difficulty of detecting weak
choline signal from a small lesion within a reason-
able time frame in a clinical setting at 1.5 T, the
sensitivity of 1H MR spectroscopy in detecting
breast malignancy drops dramatically when the
lesion is less than 2 cm in diameter (9). With
expected improvement in SNR, higher-field-
strength (eg, 3-T) MR imagers may allow 1H MR
spectroscopic investigation of smaller lesions with
high sensitivity within a reasonable time frame.
Higher field strength will also improve spectral
resolution, which means better separation be-
tween water, choline, and fat peaks. This im-
RG f Volume 27 ● Special Issue Bartella and Huang S243

Figure 1. (a) Sagittal non-fat-suppressed T1-weighted MR image (repetition time msec/

echo time msec ⫽ 6.4/3.1) of the right breast, obtained in a 65-year-old woman with a his-
tory of pseudoangiomatous stromal hyperplasia in the left breast, shows normal glandular
parenchyma and fat. (b) Magnified spectrum illustrates a high lipid (Lip) peak, but no cho-
line (Cho) resonance peak is observed at a frequency of 3.2 ppm. Lac ⫽ lactate.

Figure 2. (a) Sagittal non-fat-suppressed T1-weighted MR image (6.4/3.1) of the left

breast, obtained in a 47-year-old woman during week 2 of the menstrual cycle, shows nor-
mal glandular parenchyma and little fat. The patient had undergone lumpectomy in the con-
tralateral breast for cancer discovered at screening breast MR imaging performed owing to
the patient’s high risk. (b) Magnified spectrum illustrates a high lipid (Lip) peak, but no
choline (Cho) resonance peak is observed at a frequency of 3.2 ppm. Lac ⫽ lactate.

proved resolution would allow improved spectral
quality and less obscuration of the choline peak
by either the water peak or the fat peak.
Evaluation of Normal
and Lactating Breast Parenchyma
Normal glandular parenchyma of the breast does
not consistently demonstrate a choline resonance
peak that can be detected at 1.5 T. At our institu-
tion, we conducted a small prospective study in
which we performed 1H MR spectroscopy in 27
patients undergoing screening breast MR imaging
(10). We included both pre- and postmenopausal
patients as well as patients at different stages of
the menstrual cycle (Figs 1–5). All of these pa-
tients have undergone imaging or clinical fol-
low-up for a year, with none having developed
any abnormality at the site of spectroscopy. All
areas where the voxel was placed and 1H MR
spectroscopy was performed had MR imaging
characteristics of normal breast parenchyma with-
out evidence of suspect enhancement. We did
not detect any choline in normal breast tissue at
1.5 T.
S244 October 2007 RG f Volume 27 ● Special Issue

Figure 3. (a) Sagittal non-fat-suppressed T1-weighted MR image (6.4/3.1) of the left

breast obtained in a 53-year-old woman shows normal glandular parenchyma. The patient
had undergone lumpectomy for cancer in the right breast that was discovered at screening
breast MR imaging performed owing to the patient’s high risk. (b) Magnified spectrum il-
lustrates a high lipid (Lip) peak, but no choline (Cho) resonance peak is observed at a fre-
quency of 3.2 ppm. Lac ⫽ lactate.

Figure 4. (a) Sagittal non-fat-suppressed T1-weighted MR image (6.4/3.1) of the left

breast obtained in a 56-year-old woman shows normal glandular parenchyma and little fat.
The patient had undergone lumpectomy for atypical ductal hyperplasia that was discovered
at screening breast MR imaging performed owing to the patient’s high risk. (b) Magnified
spectrum illustrates a high lipid (Lip) peak, but no choline (Cho) resonance peak is observed
at a frequency of 3.2 ppm. Lac ⫽ lactate.

A group in Australia studied 43 asymptomatic Differentiating Benign

volunteers, including three lactating mothers, at
1.5 T (4). A resonance in the choline spectral re-
gion (3.2 ppm) was observed in all three mothers,
but three false-positive resonances were also seen
in the remaining 40 (nonlactating) volunteers.
Choline signal has also been documented in the
lactating breast by other groups (11,12). Limited
data exist, but at higher field strengths, choline
signal can be detected in normal breast tissue,
increasing the need for quantification of choline
concentrations (3). The amount of choline de-
tected in normal breast tissue at higher field
strengths has been less than in malignant lesions.
from Malignant Breast Lesions
Studies have demonstrated that MR imaging can
help detect otherwise occult breast cancers, and
this modality is playing an increasingly important
role in the clinical setting, including a role in
screening high-risk women (13–15). Because of
the lack of standardization of technique and inter-
pretation, the specificity of MR imaging has been
variable from center to center, but overall its
specificity has been relatively low, resulting in a
considerable number of benign biopsies (16 –18).
Improving the positive predictive value (PPV) of
MR imaging– based biopsy recommendations
would improve the acceptability and cost-effec-
tiveness of this imaging technique.
RG f Volume 27 ● Special Issue Bartella and Huang S245

Figure 5. (a) Sagittal non-fat-suppressed T1-weighted MR image (6.4/3.1) of the left

breast obtained in a 68-year-old woman shows normal glandular parenchyma and fat. The
patient had undergone contralateral lumpectomy for breast cancer that was discovered at
screening breast MR imaging performed owing to the patient’s high risk. (b) Magnified
spectrum illustrates a high lipid (Lip) peak, but no choline (Cho) resonance peak is observed
at a frequency of 3.2 ppm. Lac ⫽ lactate.

Findings in Selected In Vivo Single-Voxel 1H MR Spectroscopic Studies Performed on 1.5-T Imagers

True- True- False- False-

Malignant Benign Sensitivity Specificity Positive Negative Positive Negative PPV
Study* Lesions Lesions (%) (%) Findings Findings Findings Findings (%)
Roebuck et
al (19) 10 7 70 86 7 6 1 3 88
Kvistad et al
(11) 11 11 82 82 9 9 2 2 82
Cecil et al
(20) 23 15 83 87 19 13 2 4 90
Yeung et al
(21) 24 6 92 83 22 5 1 2 97
Jagannathan
et al
(12) 32 14 81 86 26 12 2 6 93
Tse et al
(22) 19 21 89 100 17 21 0 2 100
Huang et al
(7) 18 12 100 87 18 8 4 0 82
Bartella et al
(23) 31 26 100 88 31 23 3 0 91
Total 168 112 87† 87† 149 97 15 19 90†
*Numbers in parentheses indicate reference numbers.
†Average percentage.

1H MR spectroscopy has been suggested as an aimed at improving discrimination between be-

adjunct to breast MR imaging to improve the
specificity of the latter technique. Prior studies
performed on 1.5-T MR imagers have reported
sensitivities of 70%–100% and specificities of
67%–100% for breast MR spectroscopy (Table).
Multiple in vivo 1H MR spectroscopic studies
nign and malignant breast lesions have been con-
ducted at several centers (1,6,7,11,19 –22,24,25).
In a study that we conducted at our institution
(23), breast 1H MR spectroscopy had a sensitivity
of 100% and a specificity of 88%, comparing
S246 October 2007 RG f Volume 27 ● Special Issue

Figure 6. Benign fibrosis and ductal hyperplasia (true-negative findings) in a 43-year-old

woman who presented with a new palpable mass in the right breast. (a) Sagittal contrast-
enhanced fat-suppressed T1-weighted MR image (6.4/3.1) demonstrates a 4.2-cm irregular
mass (arrow). A voxel was placed around the mass. (b) Magnified spectrum shows no posi-
tive choline (Cho) resonance peak, with only a noise level at a frequency of 3.2 ppm. Lac ⫽
lactate, Lip ⫽ lipid. MR-guided biopsy followed by surgical excision revealed benign fibrosis
and ductal hyperplasia. (Fig 6 reprinted, with permission, from reference 23.)

Figure 7. Mammographically detected, biopsy-proved invasive ductal carcinoma (true-

positive finding) of the left breast in a 52-year-old woman. (a) Sagittal fat-suppressed T1-
weighted MR image (6.4/3.1) obtained immediately after the intravenous injection of gado-
linium-based contrast material shows a 1.5-cm rim-enhancing mass. A voxel was placed
around the mass. (b) Magnified spectrum illustrates a positive choline (Cho) resonance peak
at a frequency of 3.2 ppm with an SNR greater than 2. Lac ⫽ lactate, Lip ⫽ lipid. (Fig 7 re-
printed, with permission, from reference 23.)

favorably with the results of prior reports that
made use of this technique. The use of 1H MR
spectroscopy as an adjunct to breast MR imaging
would have significantly (P ⬍ .01) increased the
PPV of biopsy from 35% to 82% and might have
obviated biopsy in 57% of the 40 lesions with un-
known histologic features, with none of the can-
cers being missed. These data suggest that 1H
MR spectroscopy may be a useful supplement to
breast MR imaging, reducing the number of be-
nign biopsies without compromising the diagnosis
of breast cancer (Fig 6).
All cancers in the study described in this article
were identified at 1H MR spectroscopy; there
were no false-negative findings. A choline peak
was identified at 1H MR spectroscopy in a variety
of cancer histologies, including 16 invasive can-
cers (infiltrating ductal, infiltrating lobular, and
infiltrating mixed ductal and lobular carcinoma)
(Fig 7) and one ductal carcinoma in situ (DCIS).
RG f Volume 27 ● Special Issue Bartella and Huang S247

Figure 8. Fibroadenoma and fibroadenomatoid changes (false-positive findings) in a 43-

year-old woman with biopsy-proved DCIS. A suspect lesion was detected at MR imaging
performed to determine disease extent. (a) Sagittal contrast-enhanced fat-suppressed T1-
weighted MR image (6.4/3.1) shows regional clumped enhancement in the outer portion of
the left breast. (b) Magnified spectrum illustrates a choline (Cho) resonance peak with an
SNR greater than 2. Lac ⫽ lactate, Lip ⫽ lipid. Excision revealed fibroadenoma and fibroad-
enomatoid changes. (Fig 8 reprinted, with permission, from reference 26.)

Figure 9. Chronic inflammatory lesion with atypia (false-positive findings) in a 51-year-

old woman with a positive family history of breast cancer. The patient presented with a sus-
pect lesion that had been detected at screening breast MR imaging performed owing to the
patient’s high risk. (a) Sagittal contrast-enhanced fat-suppressed T1-weighted MR image
(6.4/3.1) of the left breast shows ductal clumped enhancement in the retroareolar region. A
voxel was placed around the area of enhancement. (b) Magnified spectrum illustrates a posi-
tive choline (Cho) resonance peak with an SNR greater than 2. Lac ⫽ lactate, Lip ⫽ lipid.
Excision of the lesion demonstrated an atypical chronic inflammatory lesion. (Fig 9 re-
printed, with permission, from reference 23.)

The latter lesion is of interest in light of prior re-
ports suggesting that DCIS may not always dem-
onstrate a choline peak (19,24). Further study
involving more DCIS lesions is essential.
This study included three false-positive find-
ings: a fibroadenoma and fibroadenomatoid
changes (Fig 8), a chronic inflammatory lesion
with atypia (Fig 9), and atypical ductal hyper-
plasia with columnar cell alteration. A false-posi-
tive choline peak has previously been reported
with a fibroadenoma (11,21); to our knowledge,
S248 October 2007 RG f Volume 27 ● Special Issue

Figure 10. Palpable, mammographically detected, biopsy-proved invasive lobular carci-

noma (true-positive finding) in the left breast of a 56-year-old woman. (a) Sagittal fat-sup-
pressed T1-weighted MR image (6.4/3.1) obtained immediately after the intravenous injec-
tion of gadopentetate dimeglumine shows a 5-cm area of regional clumped enhancement in
the 12-o’clock axis. (b) Magnified spectrum illustrates a choline (Cho) resonance peak at a
frequency of 3.2 ppm with an SNR greater than 2. Lac ⫽ lactate, Lip ⫽ lipid. (Fig 10 re-
printed, with permission, from reference 26.)

Figure 11. Non–mass-enhancing lesion (true-negative finding) in a 38-year-old woman

with a BRCA1 gene. A suspect lesion was detected at screening MR imaging. (a) Sagittal
contrast-enhanced fat-suppressed T1-weighted MR image (6.4/3.1) obtained on day 11 of
the menstrual cycle shows focal clumped enhancement in the upper inner portion of the left
breast. (b) Magnified spectrum illustrates a high lipid (Lip) peak, but no choline (Cho) reso-
nance peak is observed at a frequency of 3.2 ppm. Lac ⫽ lactate.

however, no choline peak has been reported with
the other two lesions, although the number of
published series on single-voxel breast 1H MR
spectroscopy is limited. In view of the presence of
atypia in these two lesions, excision would have
been the standard of care. Further work is neces-
sary to evaluate the prevalence and characteristics
of false-positive findings at 1H MR spectroscopy.
Enhancing lesions at MR imaging that lead to
referral for biopsy are described as either mass
enhancing or non–mass enhancing. Non–mass
RG f Volume 27 ● Special Issue Bartella and Huang S249

Figure 12. Spectroscopy of non–mass-enhancing lesions.

(a) A suspect lesion was detected at screening in the left breast
of a 20-year-old woman with a positive family history of breast
cancer. Sagittal contrast-enhanced fat-suppressed T1-weighted
MR image (6.4/3.1) shows focal clumped enhancement in the
upper inner quadrant of the left breast. A voxel was placed
around the area of enhancement. Spectroscopy did not demon-
strate a choline resonance peak. MR-guided biopsy showed fi-
broadenomatoid change and breast parenchyma. (b) Benign
findings in a 43-year-old woman with a family history of breast
cancer (sister, age 41 years) who presented with nipple discharge
and breast pain. Mammography showed dense breasts without
suspect findings. Sagittal contrast-enhanced fat-suppressed T1-
weighted MR image (6.4/3.1) of the right breast demonstrates
unilateral regional enhancement at the 12-o’clock position. A
voxel was placed around the area of enhancement. MR spectros-
copy did not demonstrate a positive choline resonance peak.
MR-guided biopsy showed benign breast parenchyma. (c) DCIS
in a 57-year-old woman who presented with bloody nipple dis-
charge from the right breast. No malignant findings were seen at
mammography. Sagittal contrast-enhanced fat-suppressed T1-
weighted MR image (6.4/3.1) of the right breast demonstrates
segmental clumped enhancement of the entire lower outer quad-
rant. A voxel was placed around the area of enhancement. Spectroscopy demonstrated a positive choline resonance
peak at a frequency of 3.2 ppm with an SNR greater than 2. MR-guided biopsy and subsequent mastectomy revealed
extensive DCIS with a high nuclear grade. (d) Fibrocystic change and ductal hyperplasia in a 60-year-old woman
with a history of lumpectomy of the right breast for DCIS. Sagittal contrast-enhanced fat-suppressed T1-weighted
MR image (6.4/3.1) of the left breast shows ductal clumped enhancement in the retroareolar region. A voxel was
placed around the area of enhancement. No choline resonance peak was detected at spectroscopy. Excision revealed
fibrocystic change and ductal hyperplasia. (Fig 12 reprinted, with permission, from reference 26.)

enhancement, defined as “enhancement of an entities but may also occur in malignancies

area that is not a mass,” may involve different-
sized areas, with internal enhancement that is dis-
crete from normal enhancing breast parenchyma
(26). Non–mass enhancement has been described
in benign hormonal changes and other benign
(27,28). Biopsy is often necessary to differentiate
benign lesions with non–mass enhancement from
cancer (Figs 10 –12). However, few data have
 S250 October 2007
addressed the application of breast 1H MR spec-
troscopy to lesions with non–mass enhancement.
Our preliminary data show that the information
obtained at 1H MR spectroscopy may decrease
the number of biopsy recommendations for be-
nign lesions with non–mass enhancement. In our
study, use of 1H MR spectroscopy as a supple-
Teaching
ment to breast MR imaging would have signifi-
Point
cantly increased the PPV of biopsy for MR imag-
ing– detected lesions with non–mass enhance-
ment from 20% to 63% and would have obviated
biopsy in 68% of lesions (29).
This hypothesis has also been evaluated at
higher field strengths; at 4 T, a retrospective,
blinded-observer performance study of 55 indi-
viduals was conducted. Performing 1H MR spec-
troscopy in addition to MR imaging improved
sensitivity and specificity for all four readers and
also improved interobserver agreement (3). These
preliminary results are very promising, although
again, larger studies are needed for further evalu-
ation.
Predicting Response
to Neoadjuvant Chemotherapy
Neoadjuvant chemotherapy, also known as pre-
operative, induction, or primary chemotherapy, is
administered prior to a definitive surgical exci-
sion. It is typically administered to patients with
locally advanced disease or large primary tumors.
These patients include those with stage 3 and
stage 4 disease with isolated ipsilateral supracla-
vicular adenopathy but no distant metastases
(30). Downstaging of disease may be achieved
with neoadjuvant chemotherapy, allowing surgi-
cal excision of inoperable lesions. Neoadjuvant
chemotherapy may allow breast conservation in
patients who would otherwise require mastec-
tomy. It can also help identify patients who are
resistant to standard chemotherapy as indicated
by the lack of response of the primary tumor and
may serve as a surrogate for assessing the re-
sponse of micrometastases and ultimately en-
hance patient survival.
An early pilot study has shown that with a
1.5-T magnet, a change in the total choline con-
centration was observed after the completion of
neoadjuvant treatment, a finding that was con-
firmed with pathologic analysis (12). A small
group of 14 patients were evaluated in this pilot
study, and detection of choline was used as the
RG f Volume 27 ● Special Issue
quantification method. A more recent pilot study
was performed on a 4-T system. In this study, 13
patients with locally advanced cancer were evalu-
ated (a) before receiving their first chemotherapy
dose, (b) 24 hours after the first dose, and (c) af-
ter the fourth dose. 1H MR spectroscopy was able Teaching
to help detect a change in the choline concentra- Point
tion from baseline within 24 hours of administra-
tion of the first dose of neoadjuvant chemo-
therapy. This change had a positive correlation
with the change in final lesion size, with a statisti-
cal significance of P ⫽ .001.
These results are indeed revolutionary, since
1H MR spectroscopy would be able to help pre-
dict clinical response in patients undergoing neo-
adjuvant chemotherapy within 24 hours of their
receiving the first dose. These results suggest that
the addition of 1H MR spectroscopy may offer a
substantial advantage over MR imaging alone in
the prediction of response to neoadjuvant chemo-
therapy (31) and may ultimately enhance patient
survival. Larger studies are being designed to fur-
ther evaluate these preliminary data.
Current Limitations
of Breast 1H MR Spectroscopy
Research concerning breast 1H MR spectroscopy
is rapidly expanding, and more and more exciting
data are being reported. Considerable progress
has been made: This technique is now well toler-
ated by patients in the clinical setting, with acqui-
sition times of approximately 10 minutes. At
present, however, breast 1H MR spectroscopy—
although promising—is not ready for clinical use.
As mentioned earlier, the single-voxel tech-
Teaching
nique, which is the most commonly used tech-
Point
nique, allows only one lesion to be examined at a
time. In addition, the lesion must be around 1
cm3 in size for the data to be meaningful. In
breast evaluation, we often have to perform bi-
opsy on much smaller lesions, and overcoming
this limitation would be extremely important.
Most of the time, more than one lesion is ques-
tioned on an MR image, so the ability to evaluate
multiple lesions or even the whole breast is some-
thing that we certainly hope to achieve in the fu-
ture.
Patients with a hematoma or a metallic clip
Teaching
must be excluded, since inhomogeneities of the
Point
magnetic field are produced that affect spectros-
copy, which must be performed in a very homo-
geneous magnetic field. Patient motion also af-
fects this technique, so that short acquisition
times are essential (Fig 13). A spectroscopist is
still needed because off-line data processing must
RG f Volume 27 ● Special Issue Bartella and Huang S251

Figure 13. Biopsy-proved invasive ductal carcinoma in the left breast of a 57-year-old
woman. (a) Sagittal contrast-enhanced fat-suppressed T1-weighted MR image (6.4/3.1)
obtained immediately after the intravenous injection of gadopentetate dimeglumine shows a
1.4-cm irregular enhancing mass. (b) Magnified spectrum illustrates no choline (Cho) reso-
nance peak at a frequency of 3.2 ppm. Lac ⫽ lactate, Lip ⫽ lipid. Patient motion during the
examination is the most likely reason for the false-negative result.

be performed (off-line processing software is References

manufacturer dependent, not standardized); a
more automated method would make MR spec-
troscopy similar to any other MR imaging se-
quence, allowing it to be performed by the MR
imaging technologist and making it much easier
to incorporate into the daily clinical routine.
Several groups are currently looking at cases of
DCIS, but data on the ability of 1H MR spectros-
copy to help detect these lesions as well as the
atypical lesions are still limited. Although all types
of invasive cancers have been detected with 1H
MR spectroscopy, larger studies are still needed
to further evaluate these preliminary data (32).
Conclusions
1H
MR spectroscopy appears to have a bright fu-
ture in the field of breast imaging. Its role in dif-
ferentiating benign from malignant lesions and in
improving the specificity of breast MR imaging
may result in fewer breast biopsies. Moreover, in
the setting of monitoring response to neoadjuvant
chemotherapy, the results to date have been ex-
tremely promising. Overcoming the current limi-
tations of 1H MR spectroscopy is primarily a
technical challenge. We hope that interest in this
technique continues to grow, thereby encourag-
ing technologic advances and participation in
clinical trials around the world. Large multicenter
trials are increasingly needed and represent a vital
step in the establishment of this technique in the
clinical setting.
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RG Volume 27 • Special Issue • October 2007 Bartella and Huang

Proton (1H) MR Spectroscopy of the Breast

Lia Bartella, MD and Wei Huang, PhD
RadioGraphics 2007; 27:S241–S252 ● Published online 10.1148/rg.27si075504 ● Content Codes:

Page S242
The diagnostic value of 1H MR spectroscopy in cancer is typically based on the detection of elevated
levels of choline compounds, choline being a marker of active tumor (2).

Page S250
1
In our study, use of H MR spectroscopy as a supplement to breast MR imaging would have
significantly increased the PPV of biopsy for MR imaging–detected lesions with non–mass
enhancement from 20% to 63% and would have obviated biopsy in 68% of lesions (29).

Page S250
1
H MR spectroscopy was able to help detect a change in the choline concentration from baseline
within 24 hours of administration of the first dose of neoadjuvant chemotherapy.

Page S250
The single-voxel technique, which is the most commonly used technique, allows only one lesion to be
3
examined at a time. In addition, the lesion must be around 1 cm in size for the data to be
meaningful.

Page S250
Patients with a hematoma or a metallic clip must be excluded, since inhomogeneities of the magnetic
field are produced that affect spectroscopy, which must be performed in a very homogeneous
magnetic field. Patient motion also affects this technique, so that short acquisition times are essential
(Fig 13).